ORGANIC LETTERS
Boric Acid Catalyzed Chemoselective Esterification of r-Hydroxycarboxylic Acids
2004 Vol. 6, No. 5 679-681
Todd A. Houston,*,† Brendan L. Wilkinson,† and Joanne T. Blanchfield‡ School of Science, Griffith UniVersity, Nathan, QLD 4111, Australia and School of Molecular and Microbial Sciences, UniVersity of Queensland, St. Lucia QLD 4072, Australia
[email protected] Received October 30, 2003 (Revised Manuscript Received January 29, 2004)
ABSTRACT
Boric acid catalyzes the selective esterification of r-hydroxycarboxylic acids without causing significant esterification to occur with other carboxylic acids. The procedure is simple, high-yielding, and applicable to the esterification of r-hydroxy carboxylates in the presence of other carboxylic acids including β-hydroxyacids within the same molecule.
Fischer esterification conditions, a strong protic acid in alcohol solvent, have been used for over a century to convert carboxylic acids to their corresponding carboxylate esters. Boron acids (i.e., boric and boronic) are useful catalysts for a number of synthetic transformations including manipulation of carbonyl-based functional groups and offer milder conditions relative to common mineral acids.1 On the basis of the affinity of boronic acids for R-hydroxycarboxylic acids in both protic2 and aprotic solvents3 and the ability of boronates to catalyze amide formation,4 we explored the possibility of using boric acid as a catalyst for selective ester formation. An example using boric acid as an esterification catalyst appeared as early as 1971,5 but this involved high temperature and an additional protic acid. Here, we show that simply †
School of Science. School of Molecular and Microbial Sciences. (1) Duggan, P. J.; Tyndall, E. M. J. Chem. Soc., Perkin Trans. 1 2002, 1325. (2) Gray, C. W., Jr.; Houston, T. A. J. Org. Chem. 2002, 67, 5426 and references therein. (3) Flores-Parra, A.; Paredes-Tepox, C.; Joseph-Nathan, P.; Contreras, R. Tetrahedron 1990, 46, 4137. (4) (a) Pelter, A.; Levitt, T. E.; Nelson, P. Tetrahedron 1970, 26, 1539. (b) Ishihara, K.; Kurihara, H.; Yamamoto, H. J. Org. Chem. 1996, 61, 4196. (c) Ishihara, K.; Kurihara, H.; Yamamoto, H. Macromolecules 2000, 33, 3511. (d) Latta, R.; Springsteen, G.; Wang, B. Synthesis 2001, 1611. (e) Yang, W.; Gao, X.; Springsteen, G.; Wang, B. Tetrahedron Lett. 2002, 43, 6339. (5) Lawrence, W. W., Jr. Tetrahedron Lett. 1971, 12, 3453. ‡
10.1021/ol036123g CCC: $27.50 Published on Web 02/11/2004
© 2004 American Chemical Society
using 10-20 mol % boric acid in alcohol solution catalyzes the esterification of R-hydroxycarboxylates selectively at ambient temperature and that other carboxylates are unreactive to these reaction conditions. As the results in Table 1 show, R-hydroxycarboxylic acids are converted to their methyl esters in excellent yields. Although sodium tetraborate and phenylboronic acid also catalyze this esterification, neither works as efficiently as boric acid at similar concentrations. The procedure is quite simple. In a typical reaction the carboxylic acid was dissolved in methanol, boric acid was added, and the reaction was stirred overnight at room temperature (18 h). When the reaction mixture was then concentrated under vacuum with mild heating (40-50 °C), the majority of the catalyst was removed as its methyl ester (trimethyl borate bp 10%) and dimer (6) While the reactions were not necessarily complete at room temperature, remaining conversion occurred during evaporation of the solvent under vacuum with heating.
Table 1. Isolated Yields from Boric Acid Catalyzed (10 mol %) Methyl Ester Synthesis (18 h, Room Temperature)
(>5%) formed when the reaction was run at 0.5 M concentration. Diluting the reaction mixtures below 0.25 M reduced the amounts of these biproducts and increased the yield of the monoester product. It is important to note that although diacids such as tartrate and malate can form esters upon prolonged reflux in alcoholic solvents, no appreciable amount (
